This study is aimed at establishing whether there is a public health hazard resulting from consumption of meat and dairy products derived from livestock feeding on tansy ragwort (Senecio jacobea), a widely dispersed plant containing the hepatotoxic pyrrolizidine alkaloids. The toxicity of milk and tissue from cows and goats will be initially determined in feeding studies with rats. We will also study the absorption, excretion, distribution and metabolism of seneciphylline and jacobine, the two principal pyrrolizidine alkaloids from tansy ragwort, in three species of laboratory animals, the rat (susceptible) and the rabbit and guinea pig (resistant), and in two species of lactating farm animals, the cow (susceptible) and the goat (resistant). Particular emphasis will be placed on isolating and characterizing reactive metabolites of the pyrrolizidine alkaloids, establishing whether covalent binding of such metabolites to tissue constituents occurs, and in establishing the biochemical mechanism(s) for toxicity of the alkaloids to mammals.